scholarly journals Therapeutic drug monitoring of small molecule kinase inhibitors in oncology in a real-world cohort study: does age matter?

2018 ◽  
Vol 84 (12) ◽  
pp. 2770-2778 ◽  
Author(s):  
Marie-Rose B.S. Crombag ◽  
Jacobine G.C. van Doremalen ◽  
Julie M. Janssen ◽  
Hilde Rosing ◽  
Jan H.M. Schellens ◽  
...  
Keyword(s):  
Cohort Study ◽  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Real World ◽  
Drug Monitoring ◽  
Kinase Inhibitors ◽  
Therapeutic Drug

scholarly journals Feasibility of Extrapolating Randomly Taken Plasma Samples to Trough Levels for Therapeutic Drug Monitoring Purposes of Small Molecule Kinase Inhibitors

2021 ◽  
Vol 14 (2) ◽  
pp. 119
Author(s):  
Ruben A. G. van Eerden ◽  
Esther Oomen-de Hoop ◽  
Aad Noordam ◽  
Ron H. J. Mathijssen ◽  
Stijn L. W. Koolen
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Trough Concentration ◽  
Drug Monitoring ◽  
Half Life ◽  
Kinase Inhibitors ◽  
Therapeutic Drug ◽  
Blood Samples ◽  
Elimination Half ◽  
Trough Levels

Small molecule kinase inhibitors (SMKIs) are widely used in oncology. Therapeutic drug monitoring (TDM) for SMKIs could reduce underexposure or overexposure. However, logistical issues such as timing of blood withdrawals hamper its implementation into clinical practice. Extrapolating a random concentration to a trough concentration using the elimination half-life could be a simple and easy way to overcome this problem. In our study plasma concentrations observed during 24 h blood sampling were used for extrapolation to trough levels. The objective was to demonstrate that extrapolation of randomly taken blood samples will lead to equivalent estimated trough samples compared to measured Cmin values. In total 2241 blood samples were analyzed. The estimated Ctrough levels of afatinib and sunitinib fulfilled the equivalence criteria if the samples were drawn after Tmax. The calculated Ctrough levels of erlotinib, imatinib and sorafenib met the equivalence criteria if they were taken, respectively, 12 h, 3 h and 10 h after drug intake. For regorafenib extrapolation was not feasible. In conclusion, extrapolation of randomly taken drug concentrations to a trough concentration using the mean elimination half-life is feasible for multiple SMKIs. Therefore, this simple method could positively contribute to the implementation of TDM in oncology.

scholarly journals Pharmacokinetic Targets for Therapeutic Drug Monitoring of Small Molecule Kinase Inhibitors in Pediatric Oncology

2020 ◽  
Vol 108 (3) ◽  
pp. 494-505 ◽  
Author(s):  
Julie M. Janssen ◽  
Thomas P. C. Dorlo ◽  
Neeltje Steeghs ◽  
Jos H. Beijnen ◽  
Lidwien M. Hanff ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Small Molecule ◽  
Pediatric Oncology ◽  
Drug Monitoring ◽  
Kinase Inhibitors ◽  
Therapeutic Drug

scholarly journals P346 Single-centre experience of ustekinumab: Therapeutic drug monitoring in Crohn’s disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S331-S333
Author(s):  
C Liefferinckx ◽  
M Fassin ◽  
D Thomas ◽  
C Minsart ◽  
A Cremer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Therapeutic Drug Monitoring ◽  
Crohn's Disease ◽  
Median Time ◽  
Real World ◽  
Drug Monitoring ◽  
Drug Exposure ◽  
Therapeutic Drug ◽  
Loss Of Response

Abstract Background Therapeutic drug monitoring (TDM) is a diagnostic tool in the monitoring of anti-TNF therapies. Yet, the benefit for TDM of new biologics such as ustekinumab (USK) is still controversial in real-world experiences. Methods This monocentric retrospective study aims to correlate USK trough levels (TLs) with clinical and endoscopic data. All patients have given written consent to the Biobank (B2011/005). Endoscopic disease was defined as quiescent in absence of endoscopic lesions, mild disease in presence of few superficial ulcerations, moderate in presence of several ulcers and severe in presence of numerous deep ulcers and/or inflammatory stenosis. 313 serum USK samples from 67 Crohn’s disease patients were used to measure USK TL (USK ELISA, apDia) while 88 samples (at week 16, and before and after optimisation) were used to measure anti-drug antibody (ADA), using a drug-tolerant affinity capture elution anti-ustekinumab assay Results Demographic and baseline data of our population are presented in Table 1. The median follow-up was 73 weeks (IQR 39–92). An optimisation due to loss of response was required in 44.8% of patients (n = 30) after a median time of 38 weeks (IQR 24–55). To evaluate the drug efficacy, an endoscopy was performed in 61% of cases at a median time of 35 weeks (IQR 27–47). TLs were 5.2 µg/ml (IQR 2.1–8.8), 1.7 µg/ml (IQR 0.3–4.3) and 2.6 µg/ml (IQR 0.6–4.1) at week 8, 16 and 24, respectively. TLs at week 8 were correlated to the induction IV dose administrated (r = 0.3, p = 0.03). At week 16, low TLs were associated with higher endoscopic activity in the follow-up (p = 0.02), although this was not the case at week 8 (p = 0.5) (Figure 1). Patients not requiring an optimisation had higher TLs in maintenance than patients requiring optimisation (2.45 µg/ml (IQR 1.3–4.4) vs. 1.15 µg/ml (IQR 0.1–2.24), p = 0.008). Obviously, optimisation significantly increased TLs (1.15 µg/ml (IQR 0.1–2.24) vs. 6.6 µg/ml (IQR 2.3–11.3), p < 0.001). ADA were undetectable in all the measured samples in maintenance. Conclusion This real-world experience confirms a drug exposure-endoscopic response relationship. Week 16 seems to be an appropriate time point to monitor drug exposure. Earlier USK TLs, at week 8, appear less valuable to be monitored due to the influence of initial IV dose. The absence of immunogenicity suggests that it is not a key driver in the loss of response.

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